Weekly symptom profiles of nonhospitalized individuals infected with SARS‐CoV‐2 during the Omicron outbreak in Hong Kong: A retrospective observational study from a telemedicine center

Abstract Omicron BA.2.2 is the dominant variant in the Hong Kong outbreak since December 31, 2021. There is no study reporting the weekly symptom profile after infection. In this retrospective study, participants who tested positive for SARS‐CoV‐2 after December 31, 2021, and registered in the telemedicine system between March 14 and May 6, 2022, were analyzed. Among registered 12 950 self‐quarantined COVID‐19‐positive patients, 11 776 symptomatic patients were included for weekly symptom profile analysis. A total of 4718 (40.1%) patients reported symptoms in the first week after a positive test, 2501 (21.2%) in the second week, 1498 (12.7%) in the third week, 1048 (8.9%) in the fourth week, and 2011 (17.1%) in over 4 weeks. Cough was the most common symptom in all participants. Patients in the first week had higher odds of reporting fever (0.206, 95% confidence interval [CI]: 0.161–0.263, p < 0.001) and sore throat (0.228, 95% CI: 0.208–0.252, p < 0.001). Patients in over 4 weeks had higher odds of reporting fatigue (1.263, 95% CI: 1.139–1.402, p < 0.001). Further, having at least two vaccine doses linked to lower odds of having fever (0.675, 95% CI: 0.562–0.811, p < 0.001), but not associated with the presence of cough and fatigue. Diabetic patients had higher odds of reporting diarrhea (1.637, 95% CI: 1.351–1.982, p < 0.001). Symptoms from Omicron infection may last for more than 4 weeks and symptom profiles vary from week to week. Vaccination and comorbidity affect the symptom profiles.

Symptoms characteristic of COVID-19 include respiratory symptoms, fever, gastrointestinal symptoms, and neurological issues. [4][5][6] But symptom profiles vary according to the virus variant, 7,8 culture and geographic location, 9 comorbidities, 9 and duration of illness. 10 Several studies on the characteristics of the Omicron variant indicate that it causes less severe illness compared to previous variants. [11][12][13][14][15] A large prospective observational study (n = 63 002) in the United Kindom in early 2022 comparing Omicron and Delta infections revealed that respiratory and systemic symptoms were high in both within 21 days after being infected, but other symptoms, except sore throat and hoarse voice, were less severe with Omicron. 15 The average duration of symptoms among Omicron cases was 6.87 days (95% confidence interval [CI]: 6.58-7.16) which is shorter than Delta cases (mean duration 8.89 days, 95% CI: 8.61-9.17). 15 A small retrospective study (n = 107) of the characteristics of Omicron infection in children (<18 years old) reported that the most prevalent symptom was fever (73.1%). 16 There are no detailed published reports on the prevalence and severity of Omicron-induced symptoms in different weeks of illness.
According to the quarantine policy in Hong Kong, persons infected with COVID-19 or in close contact should be quarantined, regardless of the presence or absence of symptoms. 17 In addition, a series of stringent social distancing measures were announced by the government during the 5th wave of the outbreak. 3

| Ethics
All patients provided informed consent at the start of the online consultation in HKBU-TCMC. All personal data were de-identified. As this retrospective study used anonymized data, no ethical approval was sought. The reporting of this study followed the recommendations of the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guideline. 17

| Statistical methods
The statistical analyses were performed using the Statistical Packages of Social Sciences for Windows (SPSS; version 27.0). Statistical significance was defined as a two-sided p-value <0.05. The clinically significant for symptom prevalence was defined as: (i) the absolute difference between comparison and control groups is ≥10%; (ii) the ratio of compared figures is greater than 2 times or less than 0.5 times; (iii) the clinically significant for symptom severity is defined as the absolute difference of symptom severity scores between two groups is greater than 1 point.   Table 1. Of the included patients, 12 010 (92.7%) reported at least one type of COVID-19 symptom and 940 (7.3%) reported no COVID-19 symptoms at the time of consultation, which could be asymptomatic or already recovered. Among 12 010 symptomatic patients, 234 (2.0%) patients were excluded from the weekly symptom profile analysis as their first positive test dates were not recorded in the system. week (43.8% vs. 16.1%, p < 0.0001), and 4.6 times higher than after 4 weeks or more (43.8% vs. 8.4%, p < 0.0001). Fever was more common in the first week, 4 times higher than in the second week (8.9% vs. 2.2%, p < 0.0001), and over 20 times higher than after 4 weeks or more (8.9% vs. 0.4%, p < 0.0001), but among some patients, fever can last for 2 weeks (2.2%) to 4 weeks (0.4%). The severity level (0-5 points) of all symptoms ranged between 2 and 3 points ( Figure 2). Cough, sputum, dry throat, and sore throat had a significant higher scores in the first week of the illness than other weeks (p < 0.05). However, the differences in scores for each symptom were not clinically significant (within 1 point).

| Weekly symptom profiles
Patients in the first week of illness had the significant higher odds of reporting cough, sputum, sore throat, diarrhea, abdominal distension, nausea, headache, muscle pain, fever, and chills than other weeks (p < 0.05) (  the only symptom that was significantly associated with over 4 weeks of illness (Figure 3).

| Association between symptom profiles and the risk factors
The association between each of the symptoms and the risk factors were analyzed by a multivariable logistic regression model, and the data are presented in Figure 4.   which could increase stress for public medical resources. As for the influence after 4 weeks, more investigation work is needed to seek whether and how these patients have more symptoms and signs.

| The characteristics between symptomatic and asymptomatic patients within 7 days after testing positive
The first and second most common symptoms within 4 weeks were cough and sputum. The third most common symptom was dry throat in the first 3 weeks, and it became fatigue from the fourth week of illness. But the prevalence of fever was low. Symptoms induced by the ancestral SARS-CoV-2 strain were predominantly fever. 5,6 Less prevalence of fever in the Omicron outbreak may be because the duration of fever was short and had generally subsided before the patient's online consultation. For the first time, the severity scores for each symptom were reported, and the average scores indicate a mild to moderate severity of symptoms within 4 weeks. It indicates the severity of Omicron-induced symptoms for those nonhospitalized quarantined patients was not serious.
Fever and sore throat were shown to be the most distinguishable symptoms for the first week, while patients who had COVID-19 for more than 4 weeks were significantly more likely to have fatigue. It is consistent with the findings from the previous study of predictors of long COVID. 10 It should be noted that long COVID can involve multiple organs and can affect many systems including, but not limited to, the respiratory, cardiovascular, neurological, gastrointestinal, and musculoskeletal systems. The symptoms of long COVID include fatigue, dyspnea, cardiac abnormalities, cognitive impairment, sleep disturbances, symptoms of posttraumatic stress disorder, muscle pain, concentration problems, and headache. 21 Future study needs to focus on long COVID induced by Omicron infection.
The results represent clinical evidence of the association of the prevalence of symptoms and risk factors including age, gender, vaccination status, and comorbidity. Age is not linearly associated with developing symptoms. Studies of other variants of SARS-Cov-2 report that greater age is a risk factor of more and more severe symptoms. 22 Our study also found that apart from cough, female patients were more likely to suffer from the majority of other symptoms, which is consistent with other studies. 23 Besides, patients with different underlying comorbidities had different odds of displaying specific symptoms. This is consistent with findings from a global study. 9 It is worth noting that patients with diabetes had the greatest chances of digestive symptoms such as diarrhea and abdominal distension. The mechanism behind this correlation is unclear and deserves further study. 24 Furthermore, vaccination status, complete or incomplete, is not associated with being asymptomatic or symptomatic patients. There   In summary, as it is known that the mutations in the SARS-CoV-2 Omicron virus have increased its transmissibility, 34 there is very limited, specific information on disease progression in those infected with the Omicron variant. 35  Importantly, this study provides evidence for a future study about Omicron-induced long COVID. Furthermore, during the COVID pandemic, telemedicine mode has been playing a major role in providing efficient, widespread medical service. Combining telemedicine with big data analysis will provide much useful evidence for medical research.

AUTHOR CONTRIBUTIONS
Jingyuan Luo and Jialing Zhang contributed equally to this study.

CONFLICT OF INTEREST
The authors declare no conflict of interest.

DATA AVAILABILITY STATEMENT
Individual, de-identified patient data can be made available at the request of investigators who propose to use the data for methodologically sound research. Data will be made available 6 months after article publication, with no end date. Requests for de-identified data should be made to the principal investigator.